NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

Silk-derived peptide nanospirals assembled by self-propelled wormlike filaments

Swirl-like nanospiral is a common structure found in free-swimming biological systems,such as microtubules and actin filaments or slender bacteria.It is desired for artificially designed dynamic nanomaterials.However,the spiral formation has rarely been reported in both engineered peptides and regenerated proteins.Herein,we report that such a unique assembly behavior can be achieved by using a fusion peptide consisting of a silk-derived peptide(i.e.,GAGAGAGY)and a hydrophobic,photoresponsive azobenzene(Azo)segment.In this fusion structure,GAGAGAGY acts as a domain that spontaneously forms an elongated filament in an aqueous solution,while Azo acts as a"light-operated switch"that can undergo photoinduced isomerization to modulate the self-propulsion forces and assembly behavior.With this design,the critical factors that affect the assembly of Azo-GAGAGAGY filament,including(i)length and flexibility of filaments;(ii)propulsion,and(iii)excluded volume interactions force the tip of the filament to wind up,can be regulated to realize the spiral formation.In addition,the configurations of Azo-GAGAGAGY filaments,such as straight nanoribbons,wavy nanoribbons,single-circle spiral,and multiple-circle spiral,can be facilely mediated by changing the preparation procedure,concentration,and pH value of Azo-GAGAGAGY solution,as these changes have significant influences on self-propulsion forces.Our findings can help in the better understanding of nonequilibrium thermodynamics and collective behavior of biological systems.The findings can be used as a guideline for the designs of nanoactuators,microswimmers,transformable microrobots,and intelligent drug carriers.